HIF in Gastric Cancer: Regulation and Therapeutic Target

Li, Mengqing; Guan, Li; Yang, Xiaodong; Wang, Yin; Lv, Guoqing; Wang, Shubin

doi:10.3390/molecules27154893

Cited by 15 publications

(6 citation statements)

References 145 publications

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“…The mounting evidence suggests that hypoxia plays a crucial role as a driving force for the progression of GC (Li et al, 2022;Lin et al, 2022;Ozcan, 2023;Xing et al, 2021). HIF-1α, a component of HIF-1, acts as a central controller governing the cellular and overall physiological adaptation to low oxygen levels (45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance

Yang,

Chen,

et al. 2024

Drug Development Research

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The role of YTHDF2 in gastric cancer (GC) is controversial. Due to the limitations of technical difficulty and experimental period, research on completely knocking out YTHDF2 is rare. Therefore, further investigations are still needed to clarify the YTHDF2's clinical significance and biological function in GC. To carry out the investigation, an analysis was performed on the expression levels of YTHDF2 in both publicly available databases and samples obtained from patients with gastric cancer. Based on the complete knockout of YTHDF2 using the CRISPR‐Cas9 system, in vivo and in vitro experiments were conducted to analyze the effects of YTHDF2 on tumor formation, radiotherapy and chemoradiotherapy resistance in GC. Our investigation revealed an increase in YTHDF2 levels in GC tissues, which was found to be associated with a negative prognosis. Under hypoxic conditions, high expression of YTHDF2 enhanced the invasion of gastric cancer cells, and high expression of YTHDF2 was associated with HIF‐1a. YTHDF2 facilitated gastric cancer cell growth in vitro and in vivo. Moreover, the results of the present study demonstrated that YTHDF2 mediated the expression of CyclinD1 and stability of CyclinD1 mRNA. CyclinD1 knockdown inhibited YTHDF2‐mediated GC cell proliferation whereas CyclinD1 overexpression ameliorated YTHDF2 knockdown‐induced inhibition of GC progression. Furthermore, YTHDF2 also promoted resistance to DDP and CTX chemotherapy, along with radiotherapy treatment for GC cells. The findings suggested that YTHDF2 expression accelerated GC progression through a potential mechanism involving CyclinD1 expression, and enhanced chemoradiotherapy resistance. This indicated that YTHDF2 could be a promising prognostic biomarker and therapeutic target for individuals diagnosed with GC.

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Section: Discussionmentioning

confidence: 99%

YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance

Yang,

Chen,

et al. 2024

Drug Development Research

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“…In gastric cancer, HIF-1α has been shown to inhibit apoptosis, while promoting proliferation, angiogenesis, metastasis, and stemness of gastric cancer cells. 23 Further, HIF-1α expression is associated with increased invasion and metastasis and reduced overall survival in gastric cancer patients. 12 Recent studies have also described non-transcriptional functions for HIF-1α that contrast with its canonical roles in carcinogenesis, via contributions to cell cycle arrest 24 , 25 and inhibition of DNA replication.…”

Section: Discussionmentioning

confidence: 99%

Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori -induced gastric injury via attenuation of both cag -mediated microbial virulence and proinflammatory host responses

Noto,

Piazuelo,

Romero-Gallo

et al. 2023

Gut Microbes

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Helicobacter pylori -induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of H. pylori -induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1α, H. pylori -infected mice were treated ± dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1α. H. pylori significantly increased proinflammatory chemokines/cytokines and inflammation in vehicle-treated mice; however, this was significantly attenuated in DMOG-treated mice. DMOG treatment also significantly decreased function of the H. pylori type IV secretion system (T4SS) in vivo and significantly reduced T4SS-mediated NF-κB activation and IL-8 induction in vitro . These results suggest that prolyl hydroxylase inhibition protects against H. pylori -mediated pathologic responses, and is mediated, in part, via attenuation of H. pylori cag -mediated virulence and suppression of host proinflammatory responses.

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“…Among them, HIF-1α enhances GC invasion and metastasis through the induction of EMT. And HIF-1α is not only a possible mediator of gastric carcinogenesis but also correlates with GC severity and poor prognosis [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

A study related to the treatment of gastric cancer with Xiang-Sha-Liu-Jun-Zi-Tang based on network analysis

Jiang,

Liu,

et al. 2023

Heliyon

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HIF in Gastric Cancer: Regulation and Therapeutic Target

Cited by 15 publications

References 145 publications

YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance

YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance

Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori -induced gastric injury via attenuation of both cag -mediated microbial virulence and proinflammatory host responses

A study related to the treatment of gastric cancer with Xiang-Sha-Liu-Jun-Zi-Tang based on network analysis

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